Fielding Andrew B, Dobreva Iveta, Dedhar Shoukat
Department of Cancer Genetics, British Columbia Cancer Research Centre of BC Cancer Agency, Vancouver, British Columbia, Canada.
Cell Cycle. 2008 Jul 1;7(13):1899-906. doi: 10.4161/cc.7.13.6204. Epub 2008 Apr 24.
Integrin-linked kinase (ILK) is a member of a multiprotein complex at focal adhesions which interacts with actin. Here, it functions as a kinase and adapter protein to regulate diverse cellular processes. Gene knockout studies have demonstrated critical roles for ILK in embryonic development and in organ and tissue homeostasis. However, ILK is overexpressed in many human cancers and experimental overexpression in non-transformed cells results in the acquisition of several oncogenic phenotypes. Proteomic based approaches to identify ILK binding partners have now identified tubulins and many centrosomal and mitotic spindle associated proteins as ILK interactors in addition to the expected focal adhesion, actin interacting, proteins. Further analysis has shown that ILK co-localizes with several of these proteins to the centrosome and inhibition or depletion of ILK causes mitotic spindle defects by disrupting Aurora A kinase/TACC3/ch-TOG interactions. Here we discuss the finding that ILK is a member of a tubulin-based multiprotein complex at the centrosome, and identify potential mechanisms by which ILK regulates the organization of the mitotic spindle. We also discuss the implications of ILK's mitotic role for cancer progression and highlight the potential use of ILK inhibitors as novel anti-mitotic chemotherapeutics.
整合素连接激酶（ILK）是粘着斑处多蛋白复合物的成员，与肌动蛋白相互作用。在此，它作为一种激酶和衔接蛋白发挥作用，以调节多种细胞过程。基因敲除研究已证明ILK在胚胎发育以及器官和组织稳态中起关键作用。然而，ILK在许多人类癌症中过度表达，在未转化细胞中的实验性过表达会导致获得几种致癌表型。基于蛋白质组学的方法来鉴定ILK结合伴侣，现已鉴定出微管蛋白以及许多中心体和有丝分裂纺锤体相关蛋白作为ILK相互作用分子，此外还有预期的粘着斑、肌动蛋白相互作用蛋白。进一步分析表明，ILK与其中几种蛋白共定位于中心体，抑制或耗尽ILK会通过破坏极光激酶A/TACC3/ch-TOG相互作用导致有丝分裂纺锤体缺陷。在此，我们讨论ILK是中心体处基于微管蛋白的多蛋白复合物成员这一发现，并确定ILK调节有丝分裂纺锤体组织的潜在机制。我们还讨论了ILK的有丝分裂作用对癌症进展的影响，并强调ILK抑制剂作为新型抗有丝分裂化疗药物的潜在用途。
